Isatoic anhydride with amidines

Meyer and Wagner reported that 4-quinazolones can also be formed by heating isatoic anhydride with amidines. They found that reaction of isatoic anhydride 38 with W,iV -diaryl formamides or W,A -diaryl acetamides 44 proceeded smoothly at moderate temperatures (120-140 °C) to give 45 along with the evolution of carbon dioxide. 

It was found inadvisable to use more than four molecules of form-amide [ (47) when R = H] per molecule of anthranilic acid and the condensation produces best results when the mixture is heated at 120 -130°C for 2 hr followed by further heating at 170°-180 C for 2 hr. Other variants of this reaction involve the use of ammonium o-acylaminobenzoates, anthranilic acid in the presence of nitriles and acetic anhydride, o-acetamidonitrile with acetic anhydride or hydrogen peroxide, anthranilic esters and aliphatic or aromatic amides or amidines, isatoic anhydride with amides or amidines, and anthranilic esters with aryl iminochlorides in acetoned The mechanism proposed by Bogert and Gotthelf has had experimental supporR and is represented in Scheme 12. 

Reaction of Anthranilic Acids or Isatoic Anhydrides with Nitriles, Imidates, Thioamides, or Amidines... 

Amidine and amine groups may be joined together to form this triazepinone ring by heating the compound with methanolic sulphuric add for 3h. The reactant is obtained by stirring isatoic anhydride (review of reactions [3008]) with an amidrazone (formally, a hydrazone of a carboxamide). 

When the Neimentowski reaction is carried out under conventional reaction conditions, the yield and purity of the product are significantly affected by the reaction temperature, reaction time, and reagent ratios. As a result, numerous variations and modifications of this reaction have appeared in the literature since its initial discovery over 100 years ago, resulting in improved yields. Variations of the anthranilic acid component inelude the use of o-acylaminobenzamides, ammonium o-acylaminobenzoates, o-aeetamino-benzonitriles, ° methyl anthranilates, acetanthranils, and isatoic anhydrides in place of anthranilic acid. Conditions wherein the amide component has been replaced with either a nitrile, imidate, " thioamide, or amidine have been reported. Reaction conditions including acetic anhydride" and alkaline peroxide were also developed. More recently, reaction conditions under microwave irradiation have been reported.Details regarding these modifications are summarized below. 

---